title: Vitamin D3 up-regulated protein 1 controls the priming phase of liver regeneration.
abstract: Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that inhibits tumor cell proliferation and cell cycle progression when overexpressed. In a previous study, we showed that VDUP1 knockout (KO) mice exhibited accelerated liver regeneration because such animals could effectively control the expression of cell cycle regulators that drive the G1-to-S phase progression. In the present study, we further investigated the role played by VDUP1 in initial priming of liver regeneration. To accomplish this, VDUP1 KO and wild-type (WT) mice were subjected to 70% partial hepatectomy (PH) and sacrificed at different times after surgery. The hepatic levels of TNF-α and IL-6 increased after PH, but there were no significant differences between VDUP1 KO and WT mice. Nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT-3) were activated much earlier and to a greater extent in VDUP1 KO mice after PH. A single injection of TNF-α or IL-6 caused rapid activation of JNK and STAT-3 expression in both mice, but the responses were stronger and more sustained in VDUP1 KO mice. In conclusion, our findings provide evidence that VDUP1 plays a role in initiation of liver regeneration.
authors.affiliation: Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Sung-Kuk
authors.initials: SK
authors.lastname: Hong
authors.forename: Won-Kee
authors.initials: WK
authors.lastname: Yoon
authors.forename: Ki-Hoan
authors.initials: KH
authors.lastname: Nam
authors.forename: In-Pyo
authors.initials: IP
authors.lastname: Choi
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Won
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D008297:Male; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012038:Regeneration; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C445672:Txnip protein, mouse; D013879:Thioredoxins; D048031:JNK Mitogen-Activated Protein Kinases
keywords: NF-κB; Vitamin D3 up-regulated protein 1; c-Jun-N-terminal kinase; partial hepatectomy; signal transducer and activator of transcription 3